The etiology of human essential hypertension remains obscure. Alterations of various renal functions have been postulated as important in the pathogenesis of this entity. Bianchi et al have developed and described a strain of genetically hypertensive rats in which the kidney is clearly involved. The proposed research will attempt to define the nature of the renal abnormality in this model. Mechanisms by which the kidney may cause and/or maintain elevated systemic pressure include: 1) abnormal sodium retention; 2) inappropriate release of renin; 3) defective production and release of vasodepressor substances. The proposed studies include micropuncture experiments to identify the site and mechanism of the salt retention noted by Bianchi. In conjunction with these studies, measurement of renal blood flow and papillary plasma flow will also be performed. The role of the renin-angiotensin system will be assessed by utilizing an angiotensin II antagonist and an angiotensin converting enzyme inhibitor. The urinary excretion of prostaglandin E will be measured as an index of renal medullary synthesis and release of this substance. The effect of prostaglandin synthesis inhibition on blood pressure in these animals will also be investigated.